Eosinophilic Esophagitis
Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated inflammatory disorder of the esophagus characterized by eosinophil-predominant infiltration of the esophageal mucosa. The pathogenesis of EoE involves an aberrant immune response, predominantly type 2 (Th2) immunity, to environmental and food antigens in genetically predisposed individuals. This response leads to the recruitment and activation of eosinophils, resulting in chronic inflammation, tissue remodeling, and fibrosis of the esophageal wall. Clinically, EoE manifests with symptoms of esophageal dysfunction, including dysphagia, food impaction, and, in children, feeding difficulties, vomiting, and failure to thrive. Over time, persistent inflammation can lead to esophageal strictures and impaired quality of life, necessitating long-term management strategies to control symptoms and prevent complications.
This type is characterized by a clear association with food or environmental allergens, often coexisting with other atopic conditions such as asthma, allergic rhinitis, and atopic dermatitis. Patients typically exhibit a history of allergic diseases, and symptoms may be exacerbated by exposure to specific allergens. The esophageal inflammation in this subtype is driven by a Th2-mediated immune response, with elevated levels of interleukins IL-4, IL-5, and IL-13, leading to eosinophil recruitment and activation.
In this type, patients do not have identifiable allergic triggers or a significant atopic history. The pathogenesis is less clearly linked to environmental or dietary antigens, and the underlying immune mechanisms may involve non-allergic pathways. Clinical presentation is similar to the allergic type, but diagnosis often requires exclusion of allergic sensitization through testing.
This subtype is defined by predominant fibrostenotic complications, such as esophageal rings, strictures, and narrowing, resulting from chronic, untreated inflammation and tissue remodeling. Patients typically present with long-standing symptoms of dysphagia and recurrent food impactions, and endoscopic findings reveal structural changes in the esophagus.
This form is marked by active eosinophilic inflammation without significant fibrostenotic changes. Patients are more likely to present with symptoms of chest pain, heartburn, and less severe dysphagia. Endoscopic findings may include linear furrows, white exudates, and mucosal edema, without evidence of stricture formation.
Eosinophilic Esophagitis has emerged as a significant cause of esophageal morbidity in both pediatric and adult populations, with increasing incidence and prevalence over the past two decades. The estimated prevalence ranges from 0.5 to 1 per 1,000 individuals in Western countries, with higher rates reported in males than females (male-to-female ratio approximately 3:1). EoE can present at any age but is most commonly diagnosed in children and young adults. There is a strong association with atopic diseases, as up to 70% of patients have a history of asthma, allergic rhinitis, or eczema. The disease is more frequently reported in Caucasian populations, though it is recognized worldwide. Familial clustering and genetic predisposition have been observed, with several susceptibility loci identified, including those in the TSLP and CAPN14 genes.
The diagnosis of Eosinophilic Esophagitis is established through a combination of clinical, endoscopic, and histopathological criteria. Patients typically present with symptoms of esophageal dysfunction, such as dysphagia, food impaction, or feeding difficulties in children. Upper endoscopy is performed to assess for characteristic findings, including linear furrows, concentric rings (trachealization), white exudates, and strictures. However, endoscopic appearance alone is not diagnostic. Multiple esophageal biopsies (usually at least six, obtained from both proximal and distal esophagus) are required to evaluate mucosal eosinophilia. The histological hallmark is the presence of at least 15 eosinophils per high-power field (eos/hpf) in esophageal mucosal samples. Other causes of esophageal eosinophilia, such as gastroesophageal reflux disease (GERD), infections, and other eosinophilic gastrointestinal diseases, must be excluded. A trial of high-dose proton pump inhibitor (PPI) therapy may be used to distinguish EoE from PPI-responsive esophageal eosinophilia. Additional diagnostic tools, such as allergy testing and esophageal functional studies, may be employed to guide management but are not required for diagnosis.
Treatment options for Eosinophilic Esophagitis include dupilumab, a monoclonal antibody that targets the interleukin-4 receptor alpha subunit, thereby inhibiting signaling of both IL-4 and IL-13, key cytokines involved in the pathogenesis of EoE; dupilumab is administered via subcutaneous injection and has demonstrated efficacy in reducing esophageal eosinophil counts and improving clinical symptoms. Budesonide, a topically active corticosteroid, is also utilized in the management of EoE, typically formulated as an oral viscous suspension or swallowed inhaler to deliver the medication directly to the esophageal mucosa; budesonide acts by reducing local inflammation and has been shown to induce histological remission and alleviate symptoms in both pediatric and adult patients.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| dupilumab (Rec INN; USAN); duplimab | 1190264-60-8 | |||
 | budesonide (Rec INN; USAN; BAN) | 51333-22-3 | C25 H34 O6 | 430.534 |
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